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(12) Patent Application Publication (10) Pub. No.: US 2012/0058208A1 Jacob (43) Pub US 2012005 8208A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0058208A1 Jacob (43) Pub. Date: Mar. 8, 2012 (54) SYNERGISTIC COMPOSITION FOR Publication Classification ENHANCING BOAVAILABILITY OF CURCUMIN (51) Int. Cl. A636/906 (2006.01) (75) Inventor: Sinnakattu Varkey Jacob, Kochi 3. 46 308: (IN) A636/898 (2006.01) (73) Assignee: SYNTHITE INDUSTRIES LTD., (52) U.S. Cl. .......................... 424/756; 424/725; 514f627 Kochi (IN) (57) ABSTRACT (21) Appl. No.: 13/083,388 The present disclosure relates to a composition to enhance the bioavailability of curcumin. In one embodiment, a composi (22) Filed: Apr. 8, 2011 tion comprising plant extracts of curcumin, Vanilla and gin ger, wherein the extracts of ginger and Vanilla are rich in (30) Foreign Application Priority Data gingerol and Vanillin respectively, is provided. In other embodiments, curcumin, and one or more items selected from Sep. 4, 2010 (IN) ............................. 999/CHFA2010 the group of Vanilla, ginger and capsaicin is provided. Patent Application Publication Mar. 8, 2012 Sheet 1 of 2 US 2012/0058208A1 38: its Patent Application Publication Mar. 8, 2012 Sheet 2 of 2 US 2012/0058208A1 xeniecessel first, is: as initiatel taskg « Catalicenpeii: , taskg & Days gie 2. US 2012/00582O8 A1 Mar. 8, 2012 SYNERGISTC COMPOSITION FOR had higher MMSE results than those who did not 13. From ENHANCING BOAVAILABILITY OF a scientific standpoint, though, this does not show whether the CURCUMIN curry caused it, or people who had healthy habits also tended to eat the curry, or some completely different relationship. CROSS-REFERENCE TO RELATED 0010 Numerous studies have demonstrated that cur APPLICATION cumin, amongst only a few other things such as high impact 0001. This application claims priority to and the benefit of exercise, learning, bright light, and antidepressant usage, has Indian Provisional Patent Application number 999/CHF/ a positive effect on neurogenesis in the hippocampus and 2010, entitled “A Synergistic Composition for Enhancing concentrations of brain-derived neurotrophic factor (BDNF), Bioavailability of Curcumin, filed Apr. 9, 2010, the contents reductions in both of which are associated with stress, depres of which are hereby incorporated by reference into the present sion, and anxiety 1415 16. Curcumin has also been application. demonstrated to be a selective monoamine oxidase inhibitor (MAOI) of type MAO-A. BACKGROUND 0011. In 2009, an Iranian group demonstrated the combi nation effect of curcumin with 24 antibiotics against Staphy 0002 1. Technical Field lococcus aureus. It was shown that in the presence of a Sub 0003. The present disclosure relates generally to a com inhibitory concentration of curcumin, the antibacterial position and related methods for providing health benefits, activities of cefixime, cefotaxime, Vancomycin and tetracy and, more particularly, to compositions and related methods cline increased against test strain 17. Curcumin's potential of ginger and Vanilla extract with curcumin to increase the anticancer effects stem from its ability to induce apoptosis in bioavailability of curcumin and inhibiting tumor growth. cancer cells without cytotoxic effects on healthy cells. Cur 0004 2. Description of Related Art cumin can interfere with the activity of the transcription fac 0005 Research in the latter half of the 20th century has tor NF-KB, which has been linked to a number of inflamma identified that curcumin has a wide range of potential thera tory diseases such as cancer 18. peutic and preventive effects. So far, these effects have not 0012. A 2009 study suggested that curcumin may inhibit been confirmed in humans. However, as of 2008, numerous mTOR complex I via a novel mechanism (19. Another 2009 clinical trials inhumans were underway, studying the effect of study on curcumin effects on cancer Stated that curcumim curcuminon numerous diseases including multiple myeloma, "modulates growth of tumor cells through regulation of mul pancreatic cancer, myelodysplastic Syndromes, colon cancer, tiple cell signaling pathways including cell proliferation path psoriasis, and Alzheimer's disease 1. way (cyclin D1, c-myc), cell survival pathway (Bcl-2, Bcl 0006. In vitro and animal studies have suggested the cur XL, cFLIP. XIAP. c-IAP1), caspase activation pathway cumin may have antitumor 23, antioxidant, anti-arthritic, (caspase-8.3.9), tumor Suppressor pathway (p53, p21) death anti-amyloid, anti-ischemic 4, and anti-inflammatory prop receptor pathway (DR4, DR5), mitochondrial pathways, and erties 5. Anti-inflammatory properties may be due to inhi protein kinase pathway (JNK, Akt, and AMPK) 20. When bition of eicosanoid biosynthesis 6. In addition, curcumin 0.2% curcumin was added to a diet given to rats or mice may be effective in treating malaria, preventing cervical can previously given a carcinogen, it significantly reduced colon cer, and may interfere with the replication of the HIV virus carcinogenesis. 7. In HIV, curcumin appears to act by interfering with the 0013 The pharmacological safety and efficacy of cur P300/CREB-binding protein (CBP). It is also hepatoprotec cumin makes it a potential compound for the treatment and tive 8. prevention of a wide variety of human diseases. In spite of its 0007. A 2008 study at Michigan State University showed efficacy and safety, curcumin has not yet been approved as a that low concentrations of curcumin interfere with Herpes therapeutic agent, and the relative bioavailability of curcumin Simplex Virus-1 (HSV-1) replication 9. The same study has been highlighted as a major problem for this. Major showed that curcumin inhibited the recruitment of RNA poly reasons contributing to the low plasma and tissue levels of merase II to viral DNA, thus inhibiting the transcription of the curcuminappear to be due to poor absorption, rapid metabo viral DNA. This effect was shown to be independent of the lism, and rapid systemic elimination. The low serum level of effect on the histone acetyltransferase activities of p300/CBP. curcuminis one of the major factors affecting its bioavailabil A 1999 University of Cincinnati study indicated that cur ity. A recent study showed that after oral administration of cumin is significantly associated with protection from infec 400 mg of curcumin to rats, only traces of unchanged drug tion by HSV-2 in animal models of intravaginal infections were found in the liver and kidney. At 30 min, 90% of cur 10. cumin was found in the stomach and Small intestine, but only 0008 Curcumin acts as a free radical scavenger and anti 1% was present at 24 hours. Once absorbed, curcumin is oxidant, inhibiting lipid peroxidation 11 and oxidative DNA metabolized rapidly in the liver and excreted out of the bio damage. Curcuminoids induce glutathione S-transferase and logical system. This seriously limits the ability of curcuminto are potent inhibitors of cytochrome P450. A 2004 UCLA reach targets distant from the gut and exert its beneficial Veterans Affairs study involving genetically altered mice Sug action. gested that curcumin might inhibit the accumulation of 0014) To improve the bioavailability of curcumin, numer destructive beta-amyloid in the brains of Alzheimer's disease ous approaches have been undertaken. The reports So far patients and also break up existing plaques associated with show that the absorption, biodistribution, metabolism and the disease 12. elimination of curcuminare the major problems that affect the 0009. There is also circumstantial evidence that curcumin bioavailaibility of curcumin. Several strategies has been tried improves mental functions. A survey of 1,010 Asians who ate to overcome these problems. The use of adjuvants (bioavail yellow curry and were between the ages of 60 and 93 showed ability enhancers) is one important means in this route. Other that those who ate the sauce “once every six months' or more methods include nanoparticle technology, encapsulation of US 2012/00582O8 A1 Mar. 8, 2012 curcumin in liposome, complexation of curcumin to form (0023 6. Srivastava, K C: Bordia A. Verma S K (April micelles and phospholipids, and the introduction of biocon 1995). “Curcumin, a major component of the food spice jugates. turmeric (Curcuna longa), inhibits aggregation and alters 00.15 Adjuvants are compounds that are concomitantly eicosanoid metabolism in human blood platelets'. Pros administered with the drug/nutraceutical so as to enhance the taglandins Leukot Essent Fatty Acids 52 (4): 223-7. bioavailability of the latter. One of the main reasons for the poor bioavailability of curcumin is glucuronidation in the (0024 7. Padma, TV (2005-03-11). “Turmeric can combat liver. The adjuvants like piperine are shown to inhibit this malaria, cancer virus and HIV. SciDev.net. metabolic pathway of glucuronidation, thus increasing the (0025 8. Marotta, F.; et al. (October 2003). “Hepatopro bioavailability of curcumin. There are several reports of other tective effect of a curcumin/absinthium compound in adjuvants that show synergetic effects when used in combi experimental severe liver injury'. Chinese Journal of nation with curcumin. Digestive Diseases (Blackwell Publishing) 4(3): 122-7. 0016 Several adjuvants are reported to enhance the bio (0026 9. Kutluay S B, Doroghazi J, Roemer ME, Triezen availability of curcumin. Concomitant administration of pip berg SJ (January 2008). “Curcumin inhibits herpes sim erine along with curcumin (Bioperin) has been shown to plex virus immediate-early gene expression by a mecha increase the bioavailability of curcumin. Piperine inhibits nism independent of p300/CBP histone acetyltransferase hepatic and intestinal glucuronidation, which is the major activity”. Virology 373 (2): 239. pathway of curcumin metabolism, thereby reducing glucu ronidation of curcumin, and Subsequently reducing the elimi (0027 10. Bourne KZ, Bourne N, Reising SF, Stanberry L. nation from the body. The human body uses glucuronidation R (1999 July). “Plant products as topical microbicide can to make a large variety of substances more water-soluble, and, didates: assessment of in vitro and in vivo activity against in this way, allows for their subsequent elimination from the herpes simplex virus type 2.
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